Modern treatment methods have led to a major improvement in the survival rate of children with Wilms' tumor. Combined therapy using surgery, radiation therapy and chemotherapy now cures more than 85% of patients. At the same time, it is recognized that all treatment forms have their risks and complications. Better understanding of the "natural history" of Wilms' tumor in its various stages and types should lead to a refinement of the methods of management so as to achieve maximum survival with the least morbidity. Groups of investigators interested in the Wilms' tumor problem have agreed to combine their efforts in a single investigation. Many institutions and researchers, both members of cooperative groups and those hitherto unaffiliated in such endeavors, have joined in this Study. The primary objectives of the first NWTS have now been achieved. It was determined that: (1) routine post-operative radiation therapy is not essential in the treatment of all patients with localized tumors that are completely removed, (2) treatment with both actinomycin-D (AMD) and vincristine (VCR) is superior to the use of either agent alone. The secondary goals also have been reached. Prognostic factors have been identified, and a histologic grading system has been developed. NWTS-2 was built on the results of NWTS-1. Preliminary data suggests that the answers to NWTS-2 questions will soon be answered: (1) short-term maintenance AMD and VCR appear to be providing good protection, and (2) adriamycin added to AMD and VCR improves results in children with more advanced disease. Review of accumulated data indicates further study of this neoplastic entity is necessary in order to define better the role of radiation therapy, and to devise better systems of management for children with unfavorable histologic types and those with metastatic disease at diagnosis.